Studies on viral leukemogenesis in wild mice have shown that these mice differ substantially from the inbred strains. First, feral mice contain many fewer chromosomally integrated MuLV related sequences than inbred mice. Second, the ecotropic virus isolates from M. hortulanus, M. m. castaneus, and M. cervicolor differ from the ecotropic MuLVs of inbred mice in their biochemical and biological properties. Third, cells of most wild mice differ from inbred mice in their susceptibility to exogenous infection by ecotropic and xenotropic MuLVs. Most feral mice carry a novel non-restrictive allele at the Fv-1 locus and some Maryland wild mice show an unusual resistance to NB-tropic virus. Cells of most feral mice, but not laboratory mice, are susceptible to xenotropic MuLVs. This trait is controlled by a single chromosome 1 locus, designated Sxv which may represent a wild mouse polymorphism of the MCF-MuLV receptor locus.